Study of Exparel Versus Epidural for Pain Control After Thoracotomy

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT02178553
• Collaborator: (none)
• Enrollment: 102
• Location: 1
• Arms: 2
• Actual Duration (Months): 51.4
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

Unilateral intercostal nerve blocks provide pain control as effectively as a continuous thoracic epidural, and will a lower incidence of side effects.

Condition or Disease	Intervention/Treatment	Phase
Pain Following Thoracotomy Surgery	Drug: Epidural; Drug: Intercostal Bupivicaine (Exparel)	Phase 4

Detailed Description

In this study we will study to see if a single set of unilateral intercostal nerve blocks provides pain control as effectively as a continuous thoracic epidural, and will a lower incidence of side effects. Although the anesthesiologists involved in providing care for patients having thoracotomy incisions at St. Mary's Hospital are experts at placing thoracic epidural catheters, this study will attempt to show that a less technically challenging procedure done by surgeons intra-operatively can provide comparable pain relief.

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Non-inferiority Trial of Continuous Thoracic Epidural Analgesia Versus Single Intercostal Nerve Block After Thoracotomy
• Actual Study Start Date: Oct 15, 2014
• Actual Primary Completion Date: Oct 9, 2018
• Actual Study Completion Date: Jan 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Epidural In the epidural catheter (TEC) group, a thoracic epidural catheter will be placed at the level of T6-T8 and advanced 5 cm into the epidural space and a 3 ml test dose of lidocaine 1.5% will be administered before the induction of general anesthesia. Patients will be excluded from the study if the catheter cannot be placed. A bolus dose of 0.5 mg hydromorphone plus 4.5 ml 0.125% bupivacaine will be administered before surgical incision. An epidural infusion of 0.075% bupivacaine and 10 mcg/ml hydromorphone, prepared by the hospital pharmacy, will be started intraoperatively at a rate of 5 ml/hr.	Drug: Epidural
Active Comparator: Intercostal bupivicaine (Exparel) In the intercostal block (ICB) group, liposomal bupivacaine 1.3% (4 ml) will injected by the surgeon under direct vision into the proximal intercostal space at the level of the thoracotomy and one interspace above and below. In addition, liposomal bupivacaine 1.3 % (4 ml) will be injected at each of the chest tube exit sites. Thus, a total of 20 ml liposomal bupivacaine 1.3% (260 mg) will be administered.	Drug: Intercostal Bupivicaine (Exparel)

Outcome Measures

Primary Outcome Measures

1. Pain Scores With Cough on First Postoperative Day [In the morning (8 am) on first postoperative day]

   Pain with cough documented using the numerical rating scale pain scores (0-10)

2. Pain Scores With Cough on the Second Postoperative Day [In the morning (8 am) on the second postoperative day]

   Pain with cough documented using the numerical rating scale pain scores (0-10). Zero indicates no pain, and 10 indicates the worst pain one could imagine.

Secondary Outcome Measures

1. Pain Scores at Rest in the Morning on the First Postoperative Day [Each morning for two days postoperative]

   NRS pain scores on a 0-10 scale at rest at 8 am on the first postoperative day. Zero indicates no pain, and 10 indicates the worst pain one could imagine.

2. Pain Scores at Rest on the Second Postoperative Day [Each morning for two days postoperative]

   NRS pain scores on a 0-10 scale at rest in the morning on the second postoperative day. Zero indicates no pain, and 10 indicates the worst pain one could imagine.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18 years and older

• Undergoing thoracotomy (lobectomy, segmentectomy, wedge resection or pneumonectomy).

Exclusion Criteria:

• Planned chest wall resection or abdominal incision and/or gastroesophageal surgery;

• Current enrollment in another post-thoracotomy analgesic research protocol; pre-existing pain syndrome (such as fibromyalgia, complex regional pain syndrome or postherpetic neuralgia in a thoracic distribution);

• Daily opioid therapy;

• Current gabapentin or pregabalin therapy;

• Allergy to any study medication; coagulation or infectious issues that would preclude epidural catheter placement;

• Severe psychological disorders or inability to understand the study protocol; -Prisoners or other institutionalized individuals;

• Severe hepatic, renal or cardiovascular disorders.

• Women who are pregnant will not be included in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55902

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: James D Hannon, MD, Mayo Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 27, 2018

More Information

Publications

None provided.

• Responsible Party: James D. Hannon, M.D., PI, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02178553
• Other Study ID Numbers: 14-002940
• First Posted: Jul 1, 2014
• Last Update Posted: Jan 9, 2020
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by James D. Hannon, M.D., PI, Mayo Clinic: Thoracotomy; Pain
• Additional relevant MeSH terms: Bupivacaine

Study Results

Participant Flow

Arm/Group Title	Epidural	Intercostal Bupivicaine (Exparel)
Arm/Group Description	In the epidural catheter (TEC) group, a thoracic epidural catheter will be placed at the level of T6-T8 and advanced 5 cm into the epidural space and a 3 ml test dose of lidocaine 1.5% will be administered before the induction of general anesthesia. Patients will be excluded from the study if the catheter cannot be placed. A bolus dose of 0.5 mg hydromorphone plus 4.5 ml 0.125% bupivacaine will be administered before surgical incision. An epidural infusion of 0.075% bupivacaine and 10 mcg/ml hydromorphone, prepared by the hospital pharmacy, will be started intraoperatively at a rate of 5 ml/hr.	In the intercostal block (ICB) group, liposomal bupivacaine 1.3% (4 ml) will injected by the surgeon under direct vision into the proximal intercostal space at the level of the thoracotomy and one interspace above and below. In addition, liposomal bupivacaine 1.3 % (4 ml) will be injected at each of the chest tube exit sites. Thus, a total of 20 ml liposomal bupivacaine 1.3% (260 mg) will be administered.
Period Title: Overall Study
STARTED	53	49
COMPLETED	45	39
NOT COMPLETED	8	10

Baseline Characteristics

Arm/Group Title	Epidural	Intercostal Bupivicaine (Exparel)	Total
Arm/Group Description	In the epidural catheter (TEC) group, a thoracic epidural catheter will be placed at the level of T6-T8 and advanced 5 cm into the epidural space and a 3 ml test dose of lidocaine 1.5% will be administered before the induction of general anesthesia. Patients will be excluded from the study if the catheter cannot be placed. A bolus dose of 0.5 mg hydromorphone plus 4.5 ml 0.125% bupivacaine will be administered before surgical incision. An epidural infusion of 0.075% bupivacaine and 10 mcg/ml hydromorphone, prepared by the hospital pharmacy, will be started intraoperatively at a rate of 5 ml/hr.	In the intercostal block (ICB) group, liposomal bupivacaine 1.3% (4 ml) will injected by the surgeon under direct vision into the proximal intercostal space at the level of the thoracotomy and one interspace above and below. In addition, liposomal bupivacaine 1.3 % (4 ml) will be injected at each of the chest tube exit sites. Thus, a total of 20 ml liposomal bupivacaine 1.3% (260 mg) will be administered.	Total of all reporting groups
Overall Participants	45	39	84
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.7 (12.5)	62.1 (10.8)	61.9 (11.7)
Sex: Female, Male (Count of Participants)
Female	19 42.2%	21 53.8%	40 47.6%
Male	26 57.8%	18 46.2%	44 52.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.2%	0 0%	1 1.2%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	43 95.6%	39 100%	82 97.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 2.2%	0 0%	1 1.2%
Body Mass Index (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	29.5 (6.1)	28.8 (7.4)	29.2 (6.7)

Outcome Measures

1. Primary Outcome

Title	Pain Scores With Cough on First Postoperative Day
Description	Pain with cough documented using the numerical rating scale pain scores (0-10)
Time Frame	In the morning (8 am) on first postoperative day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epidural	Intercostal Bupivicaine (Exparel)
Arm/Group Description	In the epidural catheter (TEC) group, a thoracic epidural catheter will be placed at the level of T6-T8 and advanced 5 cm into the epidural space and a 3 ml test dose of lidocaine 1.5% will be administered before the induction of general anesthesia. Patients will be excluded from the study if the catheter cannot be placed. A bolus dose of 0.5 mg hydromorphone plus 4.5 ml 0.125% bupivacaine will be administered before surgical incision. An epidural infusion of 0.075% bupivacaine and 10 mcg/ml hydromorphone, prepared by the hospital pharmacy, will be started intraoperatively at a rate of 5 ml/hr.	In the intercostal block (ICB) group, liposomal bupivacaine 1.3% (4 ml) will injected by the surgeon under direct vision into the proximal intercostal space at the level of the thoracotomy and one interspace above and below. In addition, liposomal bupivacaine 1.3 % (4 ml) will be injected at each of the chest tube exit sites. Thus, a total of 20 ml liposomal bupivacaine 1.3% (260 mg) will be administered.
Measure Participants	45	39
Mean (Standard Deviation) [units on a scale]	6.1 (2.7)	6.9 (2.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Epidural, Intercostal Bupivicaine (Exparel)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	We determined that a difference of 1 unit between groups would be the bound for non-inferiorty.
Statistical Test of Hypothesis	p-Value	0.142
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Confidence Interval
	Estimated Value	1
	Confidence Interval	(2-Sided) 90%; -0.1 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Pain Scores With Cough on the Second Postoperative Day
Description	Pain with cough documented using the numerical rating scale pain scores (0-10). Zero indicates no pain, and 10 indicates the worst pain one could imagine.
Time Frame	In the morning (8 am) on the second postoperative day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epidural	Intercostal Bupivicaine (Exparel)
Arm/Group Description	In the epidural catheter (TEC) group, a thoracic epidural catheter will be placed at the level of T6-T8 and advanced 5 cm into the epidural space and a 3 ml test dose of lidocaine 1.5% will be administered before the induction of general anesthesia. Patients will be excluded from the study if the catheter cannot be placed. A bolus dose of 0.5 mg hydromorphone plus 4.5 ml 0.125% bupivacaine will be administered before surgical incision. An epidural infusion of 0.075% bupivacaine and 10 mcg/ml hydromorphone, prepared by the hospital pharmacy, will be started intraoperatively at a rate of 5 ml/hr.	In the intercostal block (ICB) group, liposomal bupivacaine 1.3% (4 ml) will injected by the surgeon under direct vision into the proximal intercostal space at the level of the thoracotomy and one interspace above and below. In addition, liposomal bupivacaine 1.3 % (4 ml) will be injected at each of the chest tube exit sites. Thus, a total of 20 ml liposomal bupivacaine 1.3% (260 mg) will be administered.
Measure Participants	45	39
Mean (Standard Deviation) [score on a scale]	5.2 (2.1)	6.0 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Epidural, Intercostal Bupivicaine (Exparel)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	We determined that a difference of 1 unit between groups would be the bound for non-inferiorty.
Statistical Test of Hypothesis	p-Value	0.101
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Confidence Interval
	Estimated Value	1
	Confidence Interval	(2-Sided) 90%; 0.4 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Pain Scores at Rest in the Morning on the First Postoperative Day
Description	NRS pain scores on a 0-10 scale at rest at 8 am on the first postoperative day. Zero indicates no pain, and 10 indicates the worst pain one could imagine.
Time Frame	Each morning for two days postoperative

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epidural	Intercostal Bupivicaine (Exparel)
Arm/Group Description	In the epidural catheter (TEC) group, a thoracic epidural catheter will be placed at the level of T6-T8 and advanced 5 cm into the epidural space and a 3 ml test dose of lidocaine 1.5% will be administered before the induction of general anesthesia. Patients will be excluded from the study if the catheter cannot be placed. A bolus dose of 0.5 mg hydromorphone plus 4.5 ml 0.125% bupivacaine will be administered before surgical incision. An epidural infusion of 0.075% bupivacaine and 10 mcg/ml hydromorphone, prepared by the hospital pharmacy, will be started intraoperatively at a rate of 5 ml/hr.	In the intercostal block (ICB) group, liposomal bupivacaine 1.3% (4 ml) will injected by the surgeon under direct vision into the proximal intercostal space at the level of the thoracotomy and one interspace above and below. In addition, liposomal bupivacaine 1.3 % (4 ml) will be injected at each of the chest tube exit sites. Thus, a total of 20 ml liposomal bupivacaine 1.3% (260 mg) will be administered.
Measure Participants	45	39
Mean (Standard Deviation) [NRS pain score on a scale from 0-10]	2.9 (2.0)	4.0 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Epidural, Intercostal Bupivicaine (Exparel)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	We determined that a difference of 1 unit between groups would be the bound for non-inferiorty.
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Confidence Interval
	Estimated Value	1
	Confidence Interval	(2-Sided) 90%; 0.4 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Pain Scores at Rest on the Second Postoperative Day
Description	NRS pain scores on a 0-10 scale at rest in the morning on the second postoperative day. Zero indicates no pain, and 10 indicates the worst pain one could imagine.
Time Frame	Each morning for two days postoperative

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Epidural	Intercostal Bupivicaine (Exparel)
Arm/Group Description	In the epidural catheter (TEC) group, a thoracic epidural catheter will be placed at the level of T6-T8 and advanced 5 cm into the epidural space and a 3 ml test dose of lidocaine 1.5% will be administered before the induction of general anesthesia. Patients will be excluded from the study if the catheter cannot be placed. A bolus dose of 0.5 mg hydromorphone plus 4.5 ml 0.125% bupivacaine will be administered before surgical incision. An epidural infusion of 0.075% bupivacaine and 10 mcg/ml hydromorphone, prepared by the hospital pharmacy, will be started intraoperatively at a rate of 5 ml/hr.	In the intercostal block (ICB) group, liposomal bupivacaine 1.3% (4 ml) will injected by the surgeon under direct vision into the proximal intercostal space at the level of the thoracotomy and one interspace above and below. In addition, liposomal bupivacaine 1.3 % (4 ml) will be injected at each of the chest tube exit sites. Thus, a total of 20 ml liposomal bupivacaine 1.3% (260 mg) will be administered.
Measure Participants	45	39
Mean (Standard Deviation) [NRS pain scores on a scale from 0-10]	2.8 (1.9)	3.2 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Epidural, Intercostal Bupivicaine (Exparel)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	We determined that a difference of 1 unit between groups would be the bound for non-inferiorty.
Statistical Test of Hypothesis	p-Value	0.375
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Confidence Interval
	Estimated Value	1
	Confidence Interval	(2-Sided) 90%; -0.3 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	3 months from the date of surgery
Arm/Group Title	Epidural		Intercostal Bupivicaine (Exparel)
Arm/Group Description	In the epidural catheter (TEC) group, a thoracic epidural catheter will be placed at the level of T6-T8 and advanced 5 cm into the epidural space and a 3 ml test dose of lidocaine 1.5% will be administered before the induction of general anesthesia. Patients will be excluded from the study if the catheter cannot be placed. A bolus dose of 0.5 mg hydromorphone plus 4.5 ml 0.125% bupivacaine will be administered before surgical incision. An epidural infusion of 0.075% bupivacaine and 10 mcg/ml hydromorphone, prepared by the hospital pharmacy, will be started intraoperatively at a rate of 5 ml/hr. Epidural		In the intercostal block (ICB) group, liposomal bupivacaine 1.3% (4 ml) will injected by the surgeon under direct vision into the proximal intercostal space at the level of the thoracotomy and one interspace above and below. In addition, liposomal bupivacaine 1.3 % (4 ml) will be injected at each of the chest tube exit sites. Thus, a total of 20 ml liposomal bupivacaine 1.3% (260 mg) will be administered. Intercostal Bupivicaine (Exparel)
All Cause Mortality
	Epidural		Intercostal Bupivicaine (Exparel)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/46 (2.2%)		3/39 (7.7%)
Serious Adverse Events
	Epidural		Intercostal Bupivicaine (Exparel)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/46 (10.9%)		5/39 (12.8%)
Cardiac disorders
Myocardial infarction	0/46 (0%)		1/39 (2.6%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	4/46 (8.7%)		1/39 (2.6%)
Pulmonary complications	0/46 (0%)		2/39 (5.1%)
Surgical and medical procedures
Prolonged hospital stay	1/46 (2.2%)		1/39 (2.6%)
Other (Not Including Serious) Adverse Events
	Epidural		Intercostal Bupivicaine (Exparel)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/46 (6.5%)		0/39 (0%)
Skin and subcutaneous tissue disorders
Pruritis	3/46 (6.5%)		0/39 (0%)

Limitations/Caveats

The study was stopped before the target number of participants was achieved.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.